Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Population
2.2. Isolation of Peripheral Blood Mononuclear Cells
2.3. Purification of Total RNA and Synthesis of Complementary DNA
2.4. Primers and Quantitative Reverse Transcriptase Real-Time Polymerase Chain Reaction (qRT-PCR)
2.5. Determination of Primer Efficiency
2.6. Electrophoresis of PCR Products
2.7. Statistical Analysis
3. Results
3.1. Perforin and Granzyme B Transcripts in Recipients after Kidney Transplantation
3.2. Effect of Induction Therapies on Perforin and Granzyme B Transcripts after Transplantation
3.3. Evaluation of Predictors for Perforin/Granzyme B Transcript Ratio after Transplantation
4. Discussion
4.1. Determination of the Extent of Immunosuppression after Kidney Transplantation
4.2. Mechanisms That Regulate the Expression of Perforin and Granzyme B in Peripheral Blood Mononuclear Cells
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | Total (N = 408) |
---|---|
Recipient gender female, N (%) | 136 (33%) |
Age of recipient, years | 52 (41–62) |
Weight, kg | 81 (70–93) |
Height, cm | 175 (167–182) |
BMI, kg/m2 | 27 (23–30) |
Systolic blood pressure, mm Hg | 148 (130–160) |
Diastolic blood pressure, mm Hg | 85 (75–94) |
Cause of end-stage renal disease, N (%) | |
Glomerulonephritis | 137 (34%) |
Diabetic nephropathy | 66 (16%) |
PCKD | 58 (14%) |
Hypertensive nephropathy | 57 (14%) |
Interstitial nephritis/reflux/obstructive | 21 (5%) |
Other/unknown | 69 (17%) |
Dialysis vintage, months | 12 (3–30) |
Hemodialysis N (%) | 84 (21%) |
Peritoneal dialysis N (%) | 222 (54%) |
Preemptive transplant N (%) | 102 (25%) |
Plasma creatinine pretransplant, µmol/L | 727 (550–918) |
Plasma creatinine first postoperative day, µmol/L | 436 (288–609) |
Plasma creatinine day 29, µmol/L | 142 (113–182) |
DGF, N (%) | 51 (13%) |
Induction therapy, N (%) | |
Basiliximab | 328 (80%) |
Rituximab | 89 (22%) |
Methylprednisolone | 121 (30%) |
Thymoglobulin | 64 (16%) |
ABO-incompatible living donor N (%) | 52 (13%) |
ABO-compatible living donor N (%) | 130 (32%) |
Deceased donor N (%) | 226 (55%) |
Number of HLA mismatches, range | 3 (2–4) |
Characteristic | Blood Group AB0-Incompatible Living Donor (N = 52) | Blood Group AB0-Compatible Living Donor (N = 130) | Deceased Donor (N = 226) |
---|---|---|---|
Recipient gender female, N (%) | 13 (25%) | 47 (36%) | 76 (34%) |
Age of recipient, years | 48 (37–59) | 45 (35–57) | 57 (47–64) |
Weight, kg | 86 (75–97) | 81 (69–94) | 80 (69–91) |
Height, cm | 174 (168–184) | 176 (166–183) | 174 (167–180) |
BMI, kg/m2 | 28 (25–31) | 26 (23–30) | 27 (23–29) |
Systolic blood pressure, mm Hg | 148 (134–169) | 148 (130–162) | 147 (130–160) |
Diastolic blood pressure, mm Hg | 87 (76–96) | 88 (79–96) | 83 (74–90) |
Cause of end-stage renal disease, N (%) | |||
Glomerulonephritis | 17 (33%) | 56 (43%) | 64 (28%) |
Diabetic nephropathy | 7 (13%) | 20 (15%) | 39 (17%) |
PCKD | 6 (12%) | 12 (9%) | 40 (18%) |
Hypertensive nephropathy | 7 (13%) | 15 (12%) | 35 (15%) |
Interstitial nephritis/reflux/obstructive | 4 (8%) | 10 (8%) | 7 (3%) |
Other/unknown | 11 (21%) | 17 (14%) | 41 (18%) |
Dialysis vintage, months | 7 (0–21) | 10 (2–18) | 17 (5–36) |
Hemodialysis | 14 (27%) | 29 (22%) | 41 (18%) |
Peritoneal dialysis | 24 (46%) | 72 (55%) | 126 (56%) |
Preemptive transplant | 14 (27%) | 29 (22%) | 59 (26%) |
Plasma creatinine pretransplant, µmol/L | 721 (584–814) | 771 (622–1043) | 676 (522–861) |
Plasma creatinine first postoperative day, µmol/L | 344 (231–445) | 353 (253–513) | 507 (366–673) |
Plasma creatinine day 29, µmol/L | 119 (99–150) | 132 (113–165) | 153 (123–215) |
DGF, N (%) | 3 (6%) | 12 (9%) | 36 (16%) |
Induction therapy, N (%) | |||
Basiliximab | 28 (54%) | 104 (80%) | 196 (87%) |
Rituximab | 50 (96%) | 20 (15%) | 19 (8%) |
Methylprednisolone | 51 (98%) | 32 (25%) | 38 (17%) |
Thymoglobulin | 9 (17%) | 26 (20%) | 29 (13%) |
Number of HLA mismatches, range | 4 (3–5) | 3 (2–5) | 3 (2–4) |
Induction Therapies | Blood Group AB0-Incompatible Living Donor N = 52 | Blood Group AB0-Compatible Living Donor N = 130 | Deceased Donor N = 226 |
---|---|---|---|
Basiliximab, N (%) | 1 (2%) | 97 (75%) | 186 (82%) |
Basiliximab and prednisolone, N (%) | 1 (2%) | 3 (2%) | 10 (4%) |
Basiliximab, rituximab, and prednisolone, N (%) | 26 (50%) | 4 (3%) | 1 (0.5%) |
Rituximab and prednisolone, N (%) | 15 (29%) | -- | -- |
Rituximab, prednisolone, and thymoglobulin, N (%) | 9 (17%) | 16 (12%) | 18 (8%) |
Prednisolone and thymoglobulin, N (%) | -- | 9 (7%) | 9 (4%) |
Thymoglobulin, N (%) | -- | 1 (1%) | 2 (1%) |
Predictor | Univariable B | 95% CI | p-Value |
---|---|---|---|
Recipient age | −0.006 | −0.018–0.007 | 0.377 |
Recipient gender | −0.187 | −0.504–0.130 | 0–246 |
Systolic blood pressure | 0.0001 | −0.008–0.008 | 0.982 |
Diastolic blood pressure | 0.002 | −0.014–0.017 | 0.841 |
Relative reduction in creatinine on day 1 | 0.700 | 0.136–1.264 | 0.015 |
Donor age | 0.013 | −0.001–0.027 | 0.071 |
Donor gender | 0.227 | −0.191–0.645 | 0.286 |
HLA mismatches | 0.122 | 0.012–0.232 | 0.030 |
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Pipic, D.; Rasmussen, M.; Saleh, Q.W.; Tepel, M. Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients. Biomedicines 2024, 12, 1258. https://doi.org/10.3390/biomedicines12061258
Pipic D, Rasmussen M, Saleh QW, Tepel M. Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients. Biomedicines. 2024; 12(6):1258. https://doi.org/10.3390/biomedicines12061258
Chicago/Turabian StylePipic, Dino, Marianne Rasmussen, Qais W. Saleh, and Martin Tepel. 2024. "Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients" Biomedicines 12, no. 6: 1258. https://doi.org/10.3390/biomedicines12061258
APA StylePipic, D., Rasmussen, M., Saleh, Q. W., & Tepel, M. (2024). Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients. Biomedicines, 12(6), 1258. https://doi.org/10.3390/biomedicines12061258